Synthesis of 5-Alkynylproline Derivatives via Intramolecular Nicholas Reaction

Significance

Reported here is a Lewis acid catalyzed stereoselective synthesis of 5-alkynylproline derivative 2 from cobalt complexes of d-propargylic alcohol a-amino acid derivatives 1 via the Nicholas reaction. The reaction proceeds via an intramolecular nucleophilic attack by the amino group on a Co₂(CO)₆-propargylic cation to form the pyrrolidine ring system. Stereochemical outcome of the reaction is totally dependent on the nature of the protecting group with R^¹ = Ts and Bz giving useful diastereoselective control.